Microtubule Dynamics Flashcards
What happens to microtubules if they lose their GTP cap?
Undergo catastrophe where protofilaments peel off end
Dynamic instability of microtubules allows for what?
- Rapid change of structures and functions within cells
What dictates microtubule structure?
Guanine nucleotide status of tubulin
What structural changes occur when GTP is hydrolysed in microtubules?
- GTP-tubulin aligns in straight protofilaments
- When hydrolysed subunit interactions are weakened and protofilaments curve away from each other
Give an example of a microtubule destabilising factor
Kinesin-13, increases frequency of catastrophe
Give an example of a microtubule stabilising factor and how it has this effect
XMAP15 stabilises by suppressing catastrophes and enhances growth rate
How does EB1 only bind to growing microtubules?
It recognises the GTP cap
Why is EB1 so important to microtubules?
- Confers functional properties onto mt tip and allows recruitment of proteins
- Many proteins can bind to mt tip as they can bind to EB1
How do EB1 dimers bind to microtubules?
Via CH domains
Why are microtubules important cancer drug targets?
- Can help to inhibit cell division
- Targets rapidly dividing cells
How do microtubule stabilising cancer drugs like Taxane work?
- Bind with Mt lumen to beta-tubulin
- Stabilises lateral contacts between subunits
- Prevents loss of stability and causes overpolymerisation
How do microtubule destabilising cancer drugs like Colchicine work?
- Bind to intradimer alpha-beta tubulin interface and prevent curved to straight transition of heterodimer
How do microtubule destabilising cancer drugs like vinblastine work?
- Bind at interface between heterodimers inducing a kink
- or causes assembly of aberrant ring-like structures
